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Glossary of Terms

Glossary of Terms

A comprehensive reference of terminology used in adaptive immunology, immune repertoire analysis, and immunodiagnostics.

A

Adaptive Immunity

The branch of the immune system characterized by antigen-specific responses mediated by T and B lymphocytes. Features immunological memory and improves upon repeated exposure to the same pathogen.

Affinity Maturation

The process by which B cells in germinal centers undergo somatic hypermutation and selection, resulting in antibodies with progressively higher affinity for antigen.

Allelic Exclusion

The process ensuring that each lymphocyte expresses only one functional antigen receptor, despite having two alleles for each receptor gene.

Alloreactive

T cells or antibodies that recognize non-self MHC molecules, typically from another individual of the same species. Important in transplant rejection.

Ankylosing Spondylitis (AS)

An inflammatory arthritis primarily affecting the spine and sacroiliac joints. Strongly associated with HLA-B27.

Antigen-Presenting Cell (APC)

Cells that process and present antigens to T cells via MHC molecules. Includes dendritic cells, macrophages, and B cells.

Autoantibody

An antibody directed against self-antigens. Present in many autoimmune diseases and used as diagnostic markers.

Autoimmune Disease

A condition in which the immune system attacks the body’s own tissues due to failure of self-tolerance mechanisms.

B

B Cell Receptor (BCR)

The antigen receptor on B cells, consisting of membrane-bound immunoglobulin associated with signaling molecules Igα and Igβ.

Bulk Sequencing

Sequencing of mixed cell populations without isolating individual cells. Provides aggregate information about receptor repertoire but loses pairing information.

C

CDR (Complementarity-Determining Region)

The hypervariable loops within the variable domains of TCRs and antibodies that directly contact antigen. Each chain has three CDRs (CDR1, CDR2, CDR3).

CDR3

The third and most variable CDR, formed at the junction of V-(D)-J segments. Primary determinant of antigen specificity and the most common target for repertoire analysis.

Central Tolerance

The process of eliminating self-reactive lymphocytes during development in primary lymphoid organs (thymus for T cells, bone marrow for B cells).

Chain Pairing

Determining which α chain pairs with which β chain (TCR) or which heavy chain pairs with which light chain (BCR) from the same cell.

Clonal Expansion

The proliferation of a lymphocyte clone following antigen recognition, resulting in many daughter cells with identical receptors.

Clonal Selection Theory

The principle that antigen selects pre-existing lymphocyte clones bearing complementary receptors, which then proliferate and differentiate.

Clonality

A measure of how dominated a repertoire is by expanded clones versus evenly distributed rare clones. High clonality indicates oligoclonal or monoclonal expansion.

Clonotype

A unique receptor sequence, typically defined by V gene, J gene, and CDR3 sequence. The basic unit of repertoire analysis.

Co-occurrence

The detection of two receptor chains appearing together across multiple wells or samples, used computationally to infer chain pairing.

D

Diversity (D) Segment

Gene segments present in TCRβ, TCRδ, and immunoglobulin heavy chain loci that contribute to CDR3 diversity. Located between V and J segments.

Diversity Index

Mathematical measures (Shannon entropy, Simpson index, etc.) quantifying the variety and evenness of clonotypes in a repertoire.

E

Effector Cell

A differentiated lymphocyte actively performing immune functions (cytokine secretion, cytotoxicity, antibody production).

Epitope

The specific portion of an antigen recognized by a lymphocyte receptor or antibody. T cell epitopes are peptide fragments presented by MHC.

F

Flow Cytometry

A technique for analyzing cell populations based on their physical and fluorescent properties. Used for cell sorting and phenotyping.

G

Germinal Center

Specialized microenvironments in secondary lymphoid organs where B cells undergo affinity maturation and class switching.

Germline

The inherited, unrearranged configuration of antigen receptor genes before V(D)J recombination.

Gluten-Free Diet (GFD)

A diet excluding gluten-containing grains (wheat, barley, rye). Primary treatment for celiac disease.

H

HLA (Human Leukocyte Antigen)

The human MHC system. HLA genes encode molecules that present peptides to T cells. Different HLA alleles are associated with different disease risks.

HLA-B27

An HLA class I allele strongly associated with spondyloarthropathies including ankylosing spondylitis. Present in ~8% of general population.

I

IMBERA-seq

well-based bulk TCR/BCR sequencing assay that infers native alpha/beta or heavy/light chain pairing through compartmentalized amplification and co-occurrence analysis.

IMGT

The international ImMunoGeneTics information system. Provides standardized nomenclature and reference sequences for immune genes.

Immune Repertoire

The complete collection of antigen receptors (TCRs and BCRs) present in an individual at a given time.

Immunoglobulin (Ig)

Antibody proteins produced by B cells. Five classes: IgM, IgD, IgG, IgA, IgE.

Immunosequencing

High-throughput sequencing of immune receptor genes to characterize the repertoire.

J

Joining (J) Segment

Gene segments that join with V (and D where present) segments during V(D)J recombination to form complete variable region exons.

Junctional Diversity

Diversity generated at the junctions between gene segments during V(D)J recombination, including N- and P-nucleotide additions and deletions.

L

Limiting Dilution

A technique distributing cells at very low density (average less than 1 cell per well) to enable analysis of individual or near-individual cells.

Lymphocyte

White blood cells mediating adaptive immunity. Includes T cells, B cells, and NK cells.

M

Memory Cell

Long-lived lymphocytes generated during an immune response that provide rapid, enhanced responses upon re-encounter with antigen.

MHC (Major Histocompatibility Complex)

Genes encoding cell surface molecules that present peptide antigens to T cells. In humans, called HLA.

MHC Restriction

The requirement for T cells to recognize antigen only when presented by specific MHC molecules.

Minimal Residual Disease (MRD)

Small numbers of cancer cells remaining after treatment, detectable by sensitive molecular methods. Important for prognosis and treatment decisions.

Monoclonal

Derived from a single cell clone. A monoclonal expansion indicates a dominant clone (e.g., in malignancy).

N

N-Nucleotides

Non-templated nucleotides randomly added at V-(D)-J junctions by terminal deoxynucleotidyl transferase (TdT). Major source of junctional diversity.

Naive Cell

A mature lymphocyte that has not yet encountered its cognate antigen.

O

Oligoclonal

A repertoire dominated by a few expanded clones, intermediate between polyclonal (diverse) and monoclonal.

P

P-Nucleotides

Palindromic nucleotides generated during V(D)J recombination from asymmetric hairpin opening.

Paired Chain Analysis

Sequencing approaches that capture both chains of a receptor (α and β for TCR, heavy and light for BCR) from the same cell.

Peripheral Tolerance

Mechanisms that maintain self-tolerance among mature lymphocytes in peripheral tissues, including anergy, deletion, and regulatory T cells.

Polyclonal

A diverse repertoire with many clones of similar frequency. Typical of healthy, reactive immune responses.

R

RAG (Recombination-Activating Gene)

RAG1 and RAG2 proteins that initiate V(D)J recombination by recognizing and cutting at recombination signal sequences.

Recombination Signal Sequence (RSS)

Conserved DNA sequences flanking V, D, and J segments that are recognized by RAG proteins. Consist of heptamer and nonamer separated by 12 or 23 bp spacer.

Repertoire

See Immune Repertoire.

Richness

The total number of unique clonotypes in a sample. A basic measure of repertoire diversity.

S

Shannon Entropy

A diversity metric that accounts for both richness and evenness of clonotype distribution. Higher values indicate greater diversity.

Single-Cell Sequencing

Sequencing methods that isolate individual cells before analysis, enabling paired chain information and other single-cell features.

Somatic Hypermutation (SHM)

Point mutations introduced into immunoglobulin variable regions during germinal center reactions. Drives affinity maturation.

Spondyloarthropathy

A group of inflammatory diseases affecting the spine and other joints, including ankylosing spondylitis, psoriatic arthritis, and reactive arthritis.

T

T Cell Receptor (TCR)

The antigen receptor on T cells. Most commonly the αβ heterodimer; γδ TCR found on a minority of T cells.

TdT (Terminal Deoxynucleotidyl Transferase)

The enzyme that adds N-nucleotides at V-(D)-J junctions during recombination.

Tetramer

Fluorescently labeled MHC-peptide complexes used to identify and sort T cells specific for particular antigens.

Thymus

Primary lymphoid organ where T cells develop and undergo selection for self-MHC restriction and against strong self-reactivity.

TREC (T Cell Receptor Excision Circle)

Circular DNA byproducts of V(D)J recombination. Used as markers of recent thymic emigrants and for SCID screening.

V

V(D)J Recombination

The somatic recombination process that assembles functional antigen receptor genes from variable (V), diversity (D), and joining (J) gene segments.

Variable (V) Region

The N-terminal portion of TCR/BCR chains that contains the antigen-binding site, encoded by V and J (and D) gene segments.

V Gene

Variable gene segments encoding most of the variable region including CDR1 and CDR2.

Symbols and Numbers

αβ TCR

The predominant T cell receptor type, consisting of alpha and beta chains. Found on ~95% of peripheral T cells.

γδ TCR

An alternative T cell receptor type found on ~5% of peripheral T cells. Often involved in innate-like immunity.

12/23 Rule

The requirement that V(D)J recombination can only occur between a 12-RSS and a 23-RSS, ensuring proper segment joining.

This glossary is continually updated. Last revision: January 2025.